Background: Limited data exists on the hormonal mediators connecting metabolism and reproduction. Animal studies show that the reproductive hormone, kisspeptin, may also be important in metabolism. We investigated the effects of kisspeptin on human metabolism for the first time, to explore possible kisspeptin-mediated links between reproduction and metabolism.
Methods: We performed intravenous glucose tolerance tests (IVGTTs) in 15 healthy men (age 25±1y, BMI 22.3±0.5 kg.m−2); during 1 nmol.kg−1.hr−1 kisspeptin infusion and vehicle infusion. Blood samples were collected pre- and during infusions (pre-glucose load/pre-meal), when kisspeptin levels had plateaued, to determine kisspeptins effects on serum metabolites. Static incubation experiments were performed using human donor islet cells (n=6) and a human pancreatic β-cell line (EndoC-βH1 cells), to assess in vitro effects of kisspeptin on glucose-stimulated insulin secretion (GSIS).
Results: During IVGTTs, GSIS was higher with kisspeptin infusion compared to vehicle (mean serum insulin concentration kisspeptin minus vehicle: 4.1 μU.mL−1, P=0.01; disposition index: kisspeptin 2768±484 vs vehicle 2061±255, P<0.05). Consistent with this and providing mechanistic information, kisspeptin elicited dose-dependent increases in insulin secretion in vitro, in human islet and EndoC-βH1 cells. Compared to vehicle, kisspeptin resulted in changes in serum metabolites, including alterations in lysophosphatidylcholines, phosphocholines and sphingomyelins, which are associated with insulin secretion.
Conclusions: This is the first study to examine the effects of kisspeptin on metabolism in vivo in humans. We demonstrate that kisspeptin increases GSIS and produces changes in circulating metabolites, providing evidence for novel kisspeptin-mediated connections between reproduction and metabolism. This has significant implications for the ongoing development of kisspeptin-based therapies: in addition to treating reproductive disorders kisspeptin may also have positive effects on associated metabolic dysfunction (for example in men with type 2 diabetes, up to 40% of whom have associated hypogonadism).
19 Nov 2018 - 21 Nov 2018